Elsevier

Physiology & Behavior

Volume 164, Part B, 1 October 2016, Pages 488-493
Physiology & Behavior

Review
Reshaping the gut microbiota: Impact of low calorie sweeteners and the link to insulin resistance?

https://doi.org/10.1016/j.physbeh.2016.04.029Get rights and content

Highlights

  • Diet can influence the gut microbiota profile.

  • The gut microbiome is a factor contributing to obesity and insulin resistance.

  • Artificial sweeteners may perturb gut microbiota – contributing to metabolic disease.

  • Further studies examining the influence of sweeteners on metabolism are needed.

Abstract

Disruption in the gut microbiota is now recognized as an active contributor towards the development of obesity and insulin resistance. This review considers one class of dietary additives known to influence the gut microbiota that may predispose susceptible individuals to insulin resistance - the regular, long-term consumption of low-dose, low calorie sweeteners. While the data are controversial, mounting evidence suggests that low calorie sweeteners should not be dismissed as inert in the gut environment. Sucralose, aspartame and saccharin, all widely used to reduce energy content in foods and beverages to promote satiety and encourage weight loss, have been shown to disrupt the balance and diversity of gut microbiota. Fecal transplant experiments, wherein microbiota from low calorie sweetener consuming hosts are transferred into germ-free mice, show that this disruption is transferable and results in impaired glucose tolerance, a well-known risk factor towards the development of a number of metabolic disease states. As our understanding of the importance of the gut microbiota in metabolic health continues to grow, it will be increasingly important to consider the impact of all dietary components, including low calorie sweeteners, on gut microbiota and metabolic health.

Introduction

On any given day, it is estimated that 11% of healthy-weight, 19% of overweight, and 22% of obese adults drink diet beverages, prevalent products containing low calorie sweeteners [5]. Women and children are now reported to be the greatest consumers of low calorie sweeteners in the United States. In 2008, it was estimated that nearly 15% of children and 33% of women consume food and beverages containing low calorie sweeteners, a large increase compared to 1999–2000 intake reports [68]. With obesity continuing to rise on a global scale [77], low calorie sweeteners have become a popular sugar substitute, particularly in ‘diet’ and ‘light’ foods, allowing a variety of products to retain their palatability without the associated calories, creating a perception of a ‘healthier’ product. Low calorie sweeteners are ubiquitous within current food products, such as desserts, gum, breakfast foods, and (diet) beverages, and therefore may be unintentionally consumed. For example, saccharin, sucralose, and acesulfame-potassium have all been found in the breast milk of women who did not explicitly report consuming these low calorie sweeteners [69].

The three most popular low calorie sweeteners are sucralose, followed by acesulfame-potassium and aspartame [82]. Although the common characteristic of low calorie sweeteners is to provide sweetness without associated calories, it is important to note that each one is metabolically and chemically distinct. For example, sucralose is a chlorinated disaccharide of which 65–95% is excreted in feces, whereas aspartame is a dipeptide and the majority is hydrolyzed into its three moieties (phenylalanine, methanol, and aspartic acid) and absorbed within the small intestine [50], [53]. Acesulfame potassium is an acidic cyclic sulphonamide derivative and is primarily excreted in urine [52].

Low calorie sweeteners have been approved for human consumption by regulatory agencies worldwide [24], [27] and found to be ‘safe’ for human consumption. Although low calorie sweeteners may have value in reducing the energy density of the diet, their impact on health requires further investigation. There is growing recognition that ‘safe’ and ‘healthy’ are different considerations. While safety considers disease (e.g. causative in cancer) and/or injury (e.g. toxicity), healthy implies a continued state of optimal physiological functioning (e.g. lack of insulin resistance). However, there is accumulating evidence that changes in gut microbiota may contribute to the development of certain diseases in susceptible individuals, as discussed below. Therefore, observations that low calorie sweetener consumption may result in alterations in the gut microbiota calls to question whether they may still be classified as ‘safe’.

Section snippets

Epidemiological data

Epidemiological, observational and biomedical evidence show regular low calorie sweetener consumption over a prolonged period may promote obesity, glucose intolerance, and its related comorbidities [17], [20], [41], [46]. Swithers evaluated and summarized longitudinal prospective cohort studies that examined low calorie sweetened beverage consumption in relation to health outcomes, including weight change, type 2 diabetes, cardiovascular disease and the metabolic syndrome [67]. In this paper,

Gut microbiota

Collectively, the human gut consists of trillions of microorganisms, a number far exceeding the total number of our somatic cells [40], [55]. The dynamic and diverse microorganisms that inhabit the gut are capable of quick adaptation to varied pathological, dietary and metabolic conditions. This is evident in examination of its biochemical capabilities; the human microbiota has evolved to contain upwards of 60,000 glycoside hydrolases and polysaccharide lyases that are capable of digesting

Involvement of the gut microbiota in obesity and insulin resistance

The severity and prevalence of obesity has dramatically increased on a global scale, and nearly 39% and 13% of adults are now considered overweight or obese respectively [78]. These statistics are cause for concern since obesity is a known contributor to many chronic disease states including type 2 diabetes and cardiovascular disease, which is increasing in developed and developing countries alike [78]. There is now abundant evidence that the microbiota is an environmental factor actively

Low calorie sweeteners and the gut microbiota

Our inherent craving for sweet foods starts at birth and is shared with many other animal species [43]. Some of the best work to recognize an impact of low-calorie sweeteners on both feeding behaviour and the gut microbiota is derived from the agricultural sector where low calorie sweeteners are added to starter feeds. Although results are variable, the inclusion of either sugar based sweeteners or low calorie sweeteners in a number of species helps to establish gut microbiota and modulate

Potential mechanistic considerations and knowledge gaps

At present, the exact mechanisms by which low calorie sweeteners perturb the gut microbiota are not known. Although we have grouped sweeteners into one class in this review, it is important to recognize that each one has a distinct structure, metabolism and acceptable daily intake level. Going forward, studies assessing each individual sweetener and their impact in health, pregnancy, and metabolic disease states are required. In this section we briefly highlight the potential mechanisms that

Conclusions

Accumulating evidence suggests that low calorie sweetener consumption perturbs the gut microbiota and disrupts metabolic health in susceptible individuals. This concern was echoed by the US Scientific Report of the 2015 Dietary Guidelines Advisory Committee that provides the US Federal government with a foundation for developing national nutrition policy. These recommendations acknowledge a potential relationship between low calorie sweetened soft drinks and type 2 diabetes risk. Their

Conflicts of interest

The authors have no conflicts of interest to declare.

Acknowledgements

J. S. and R. A. R. (RGPIN 238382-2011) receive research funding from the National Science and Engineering Research Council of Canada. J.E.N. is supported by an Alberta Children's Hospital Research Institute Studentship (Calgary, AB).

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